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TGF-ß prevents self-reactive B cell activation

No. 39c2e | 29/08/2014

transforming growth factor beta
© Wikimedia

T follicular helper (TFH) cells contribute to the establishment of humoral immunity by controlling the delivery of helper signals to activated B cells. However, TFH development must be restrained, as aberrant accumulation of these cells is associated with positive selection of self–reactive germinal center B cells and autoimmunity in both humans and mice.

Dr. Julien C. Marie, head of a Helmholtz-Inserm Unit at Lyon and member of the German Cancer Research Center (DKFZ), revealed together with his colleague Dr. Mark J. Mc Carron that TGF-ß signaling in T cells prevents TFH cell accumulation, self-reactive B cell activation, and autoantibody production.

Using mice with either T cell-specific loss of or constitutive activation of TGF-ß signaling, they demonstrated that TGF-ß signaling is required for the thymic maturation of CD44+ CD122+ Ly49+ CD8+ regulatory T cells (Tregs), which induce TFH apoptosis and thus regulate this population.

Moreover, peripheral TFH cells escaping TGF-ß control were resistant to apoptosis, exhibited high levels of the anti-apoptotic protein BCL-2, and remained refractory to regulation by CD8+ Tregs. The unrestrained accumulation of TFH cells in the absence of TGF-ß was dependent on T cell receptor (TCR) engagement and required B cells.

Together their data revealed that TGF-ß signaling restrains TFH cell accumulation and B cell-associated autoimmunity and thereby controls self-tolerance.

The Helmholtz-Inserm unit, jointly founded by the Helmholtz-Association, Inserm and the DKFZ, is full part of the tumor immunology research program of the DKFZ. It is based at the CRCL (Cancer Research Center) of Lyon, France.

Mark J. McCarron and Julien C. Marie: TGF-ß prevents T follicular helper cell accumulation and B cell autoreactivity. Journal of Clinical Investigation 2014, DOI: 10.1172/JCI76179

The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institution in Germany. More than 1,300 scientists at the DKFZ investigate how cancer develops, identify cancer risk factors and search for new strategies to prevent people from developing cancer. They are developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to all questions on cancer.

Jointly with partners from the university hospitals, the DKFZ operates the National Center for Tumor Diseases (NCT) in Heidelberg and Dresden, and the Hopp Children's Cancer Center KiTZ in Heidelberg. In the German Consortium for Translational Cancer Research (DKTK), one of the six German Centers for Health Research, the DKFZ maintains translational centers at seven university partner locations. NCT and DKTK sites combine excellent university medicine with the high-profile research of the DKFZ. They contribute to the endeavor of transferring promising approaches from cancer research to the clinic and thus improving the chances of cancer patients.

The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.

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